Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Mavurapu Satyanarayana; Wei Feng; Liang Cheng; Angela A. Liu; Yuan Chin Tsai; Leroy F. Liu; Edmond J. LaVoie

doi:10.1016/j.bmc.2008.06.046

Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Mavurapu Satyanarayana, Wei Feng, Liang Cheng, Angela A. Liu, Yuan Chin Tsai, Leroy F. Liu, Edmond J. LaVoie

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

Original language	English
Pages (from-to)	7824-7831
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2008.06.046
Publication status	Published - Aug 15 2008
Externally published	Yes

Keywords

Antitumor
Athymic mice
Cinnolines
Cytotoxicity
Human tumor xenografts
Isoquino[4,3-c]cinnolin-12-ones
Multidrug resistance
Topoisomerase

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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10.1016/j.bmc.2008.06.046

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Satyanarayana, M., Feng, W., Cheng, L., Liu, A. A., Tsai, Y. C., Liu, L. F., & LaVoie, E. J. (2008). Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31). Bioorganic and Medicinal Chemistry, 16(16), 7824-7831. https://doi.org/10.1016/j.bmc.2008.06.046

Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31). / Satyanarayana, Mavurapu; Feng, Wei; Cheng, Liang et al.
In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 16, 15.08.2008, p. 7824-7831.

Research output: Contribution to journal › Article › peer-review

Satyanarayana, M, Feng, W, Cheng, L, Liu, AA, Tsai, YC, Liu, LF & LaVoie, EJ 2008, 'Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)', Bioorganic and Medicinal Chemistry, vol. 16, no. 16, pp. 7824-7831. https://doi.org/10.1016/j.bmc.2008.06.046

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title = "Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)",

abstract = "Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.",

keywords = "Antitumor, Athymic mice, Cinnolines, Cytotoxicity, Human tumor xenografts, Isoquino[4,3-c]cinnolin-12-ones, Multidrug resistance, Topoisomerase",

author = "Mavurapu Satyanarayana and Wei Feng and Liang Cheng and Liu, {Angela A.} and Tsai, {Yuan Chin} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",

year = "2008",

month = aug,

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doi = "10.1016/j.bmc.2008.06.046",

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AU - Satyanarayana, Mavurapu

AU - Feng, Wei

AU - Cheng, Liang

AU - Liu, Angela A.

AU - Tsai, Yuan Chin

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

AB - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

KW - Antitumor

KW - Athymic mice

KW - Cinnolines

KW - Cytotoxicity

KW - Human tumor xenografts

KW - Isoquino[4,3-c]cinnolin-12-ones

KW - Multidrug resistance

KW - Topoisomerase

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Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

Abstract

Keywords

ASJC Scopus subject areas

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